This preliminary report focuses on the therapeutic role of interferon in a large randomized trial evaluating combination chemotherapy induction and interferon maintenance, as compared with no maintenance therapy, in patients with newly diagnosed multiple myeloma. The trial also included an evaluation of the combination of interferon and dexamethasone therapy for patients who failed to respond to induction chemotherapy or who had achieved only a partial remission. Case accrual is completed for remission induction with 505 eligible patients registered on study, but is still open for additional maintenance registrations. As of January 1991, 161 patients have been randomized to interferon versus observation, but the therapeutic results of this aspect of the study remain coded. Toxicity of interferon maintenance was generally of a mild to moderate degree, and less severe than that of the interferon/dexamethasone combination, which was due to the addition of steroid side effects. Among 41 patients who failed to achieve remission with chemotherapy, 13 (32%) achieved at least a partial remission with interferon/dexamethasone, and only five others (12%) have had progressive disease. Of 12 partial responders on induction chemotherapy, five (42%) achieved remission (75% tumor regression) with interferon/dexamethasone. To date, more than 65% of patients receiving interferon/dexamethasone remain alive, suggesting that this regimen will be useful for patients who fail to achieve remission with induction chemotherapy.